Flucytosine Primary Resistance in Candida Species and Cryptococcus neoformans

 The in vitro activity of flucytosine (5FC) against 1,140 clinical isolates of Candida spp. and Cryptococcus neoformans was evaluated and compared with the activity of amphotericin B, fluconazole and itraconazole. Overall, 87.72% (1,000/1,140) of yeasts were susceptible to 5FC. This agent showed less potent in vitro activity against Candida glabrata, Candida krusei, Candida guilliermondii and Cryptococcus neoformans (MIC90s, 8–16 μg/ml) and intermediate activity or resistance to 6.5% of Candida albicans, 5.1% of Candida tropicalis and 0.8% of Candida parapsilosis strains. Amphotericin B showed potent activity against isolates with an MIC of 5FC≥8 μg/ml. A total of 112 of 140 strains that were 5FC-intermediate or -resistant showed decreased susceptibility to azoles (P<0.01).     

In vitro activity of voriconazole and other antifungal agents against clinical isolates of <Emphasis Type="Italic">Candida glabrata</Emphasis> and <Emphasis Type="Italic">Candida krusei</Emphasis>

The antifungal susceptibility of 309 Candida glabrata and 63 Candida krusei clinical isolates was tested via the Sensititre YeastOne-3 system (Trek Diagnostic Systems, East Grinstead, UK) to compare the in vitro activity of voriconazole with that of five other antifungal agents (amphotericin B, fluconazole, itraconazole, ketoconazole, and flucytosine). Voriconazole was highly active (MIC90, 0.5 g/ml) against isolates of both species, including those for which the MICs of itraconazole and fluconazole were high (MIC90s of itraconazole, 2 g/ml for C. glabrata and 0.5 g/ml for C. krusei; MIC90s of fluconazole, 32 g/ml for C. glabrata and 64 g/ml for C. krusei). Ketoconazole MIC90 values for both species were identical to those of voriconazole. The MIC90 of amphotericin B was similar for both species (0.125 g/ml for C. glabrata and 0.25 g/ml for C. krusei). As expected, flucytosine was only moderately active against C. krusei isolates (MIC90, 16 g/ml) but was highly active against C. glabrata isolates (MIC90, 0.03 g/ml). Potential cross-resistance within the azole class was noted for some strains of C. glabrata (5.5%) that presented high MIC values for all the azoles tested. In order to consider voriconazole a viable alternative to other triazoles for the treatment of infections caused by Candida species, susceptibility testing of all clinically significant isolates of C. glabrata and C. krusei is recommended because of the potential for azole cross-resistance. The Sensititre YeastOne-3 seems to be a suitable commercial tool for this purpose.     

Comparative in vitro activity of cefpiramide,a new parenteral cephalosporin

The in vitro activity of cefpiramide was compared with that of nine other cephalosporins by determining the MIC values by means of an agar dilution method for 300 representative clinical isolates of non-fastidious bacteria. Cefpiramide had a broad-spectrum of activity, similar to that of the third-generation cephalosporins. As judged by the MIC50 and the MIC90 values, cefpiramide was one of the most active cephalosporins againstPseudomonas aeruginosa (MIC50 2.9 µg/ml, MIC90 64 µg/ml), staphylococci (MIC50 1.2 µg/ml, MIC90 10 µg/ml) andEnterococcus faecalis (MIC50 13 µg/ml, MIC90 43 µg/ml). Cefpiramide had moderate activity againstEnterobacteriaceae (MIC50 4 µg/ml, MIC90 108 µg/ml), comparable to that of the older second-generation cephalosporins. Ticarcillin-resistant strains of gram-negative rods were inhibited by higher concentrations of cefpiramide than ticarcillin-susceptible strains.     

Comparative in vitro activity of cefdinir (CI-983; FK-482) against staphylococci,gram-negative bacilli and respiratory tract pathogens

The in vitro activity of cefdinir (CI-983; FK-482), a new oral cephalosporin, was compared with that of other antimicrobial agents against clinical isolates of staphylocci, gram-negative bacilli and common respiratory tract pathogens. Cefdinir (MIC90 2.0 µg/ml) was more active than cefixime (MIC90 >64 µg/ml) and equally as active as cefuroxime (MIC90 2.0 µg/ml) against oxacillin-susceptible staphylococci. Cefdinir was active againstHaemophilus influenzae, including -lactamase producers (MIC90 0.5 µg/ml),Moraxella catarrhalis (MIC90 0.12 µg/ml),Streptococcus pneumoniae (MIC90 0.06 µg/ml) andStreptococcus pyogenes (MIC90 0.06 µg/ml). The activity of cefdinir against gram-negative bacilli was variable; organisms with chromosomal cephalosporinases were often resistant.     

In vitro comparison of cilofungin alone and in combination with other antifungal agents against clinical isolates ofCandida species

Cilofungin, a lipopeptide antifungal agent, was tested for in vitro activity alone and in combination with ketoconazole, itraconazole, flucytosine and amphotericin B against 102 clinical isolates ofCandida species. At 48 hours all isolates ofCandida albicans, Candida tropicalis, Candida paratropicalis andCandida glabrata were inhibited by 5 mcg/ml of cilofungin. In contrast, the MIC90 forCandida krusei was 10 mcg/ml and forCandida parapsilosis >40 mcg/ml. The interaction of combinations of cilofungin with amphotericin B, itraconazole, ketoconazole and flucytosine was additive or indifferent at 48 hours for 100 %, 88 %, 78 % and 70 % of allCandida species isolates, respectively. Overall, cilofungin demonstrated good activity in vitro against mostCandida species isolates.     

Comparative in vitro activity of the new quinolone sparfloxacin (CI-978, AT-4140) against nosocomial gram-negative bloodstream isolates

The in vitro activity of sparfloxacin (CI-978, AT-4140), a new quinolone which is active against gram-negative and gram-positive bacteria, and nine other broad-spectrum antibiotics was tested against 128 gram-negative nosocomial bloodstream isolates from separate patients. Sparfloxacin and ciprofloxacin were among the most potent antibiotics againstEscherichia coli (n=40),Enterobacter cloacae (n=18),Klebsiella oxytoca (n=13), andKlebsiella pneumoniae (n=19), with MIC90 values of 0.25 µg/ml. Ciprofloxacin was slightly more potent than sparfloxacin againstSerratia marcescens (n=14), the MIC90 values being 0.25 and 1.0 µg/ml respectively, although all strains were susceptible to both agents. Sparfloxacin was slightly less potent than ciprofloxacin againstPseudomonas aeruginosa (n=24), the MIC90 values being 4.0 and 0.5 µg/ml respectively. Overall, the in vitro activity of sparfloxacin compared favorably with that of ciprofloxacin and the other broad spectrum agents tested against nosocomial gram-negative bloodstream isolates.     

In vitro activity and beta-lactamase stability of the new oral cephalosporin Bay v 3522

The activity of the new oral cephalosporin Bay v 3522 was compared to that of six other beta-lactam agents. Bay v 3522 inhibited methicillin-susceptibleStaphylococcus aureus andStaphylococcus epidermidis at 2 µg/ml, compared to MICs of 8 µg/ml for the other cephalosporins tested. It was more active againstStreptococcus pyogenes (MIC 0.06 µg/ml) than cefuroxime, cefixime, cephalexin and cefaclor. Groups B, C and G streptococci were inhibited at 0.12 µg/ml, while the MIC90 forStreptococcus bovis and viridans streptococci was 0.5 and 2 µg/ml, respectively. The MIC90 for enterococci andListeria monocytogenes was 8 µg/ml.Clostridium perfringens was inhibited by 0.12 µg/ml, but mostBacteroides spp. were resistant. The MIC90 for beta-lactamase positiveEscherichia coli (producing primarily TEM-1) was >64 µg/ml and for beta-lactamase negative strains 16 µg/ml. The MIC90 for high-level beta-lactamase producingKlebsiella pneumoniae was >64 µg/ml versus 4 µg/ml for other isolates. The MIC90 forMoraxella catarrhalis was 2 µg/ml, forHaemophilus influenzae 1 µg/ml, and forNeisseria gonorrhoeae 4 µg/ml.Enterobacter cloacae, Citrobacter freundii, Proteus mirabilis, Providencia spp. andPseudomonas aeruginosa were resistant. Bay v 3522 was destroyed by TEM-1, SHV-1, TEM-3 and P99 beta-lactamases.     

Multicentre comparative study on the antibacterial activity of FK-037, a new parenteral cephalosporin

The in vitro antibacterial activity of FK-037, a new parenteral cephalosporin structurally related to cefpirome and cefepime, was compared with that of cefotaxime, ceftazidime, aztreonam, cefpirome, cefepime, imipenem and meropenem against 1,837 clinical isolates obtained from three Spanish hospitals. FK-037 inhibited 90 % ofEnterobacteriaceae isolates at 0.25 µg/ml, with the exception ofEnterobacter aerogenes (MIC90 1 µg/ml),Enterobacter cloacae andCitrobacter freundii (MIC90 8 µg/ml). In cefotaxime-and ceftazidime-resistantKlebsiella pneumoniae strains producing SHV-2 and SHV-6 -lactamases, the activity of FK-037, cefpirome and cefepime was similar (MIC range 0.25–32 µg/ml). InEnterobacteriaceae strains hyperproducing chromosomally inducible -lactamases, FK-037 (MIC90 range, 0.25–8 µg/ml) was 8- to 16-fold more active than cefotaxime and ceftazidime but two- to eightfold less active than cefpirome and cefepime. FK-037 and cefpirome were twofold more active than ceftazidime and cefepime againstPseudomonas aeruginosa isolates, with MIC90 values of 16 µg/ml. The activity of FK-037, cefpirome and cefepime was two- to eightfold lower in ceftazidime-resistant derepressedPseudomonas aeruginosa mutants. FK-037 (MIC range, 0.12–2 µg/ml) and the other -lactam agents tested were active against methicillin-susceptible staphylococci; however, only cefpirome and, particularly, FK-037 (MIC90 of 32 µg/ml) displayed some activity against methicillin-resistant strains. In penicillin-susceptible,-intermediate and -resistantStreptococcus pneumoniae isolates, the MIC90s of FK-037 were 0.03, 0.5 and 1 µg/ml, respectively. The corresponding values forStreptococcus viridans isolates were 0.12, 1 and 8 µg/ml, respectively. In bothStreptococcus pneumoniae andStreptococcus viridans isolates, FK-037 displayed activity similar to that of cefotaxime and cefpirome and slightly higher than that of cefepime.     

In vitro activity of the new glycopeptide decaplanin

The activity of decaplanin, a new glycopeptide, was compared to that of vancomycin, teicoplanin and daptomycin. Decaplanin was two- to four-fold less active than vancomycin, teicoplanin and daptomycin againstStaphylococcus aureus andStaphylococcus epidermidis, with an MIC90 of 2 µg/ml for methicillin-susceptible and 4 µg/ml for methicillin-resistant isolates. Decaplanin had activity similar to that of vancomycin againstStreptococcus pyogenes, Streptococcus agalactiae, group C and G streptococci, with an MIC90 of 0.12 µg/ml. It was less active than the other agents against the viridans group streptococci (MIC90 4 µg/ml). The activity of decaplanin against enterococci (MIC90 4 µg/ml) was similar to that of vancomycin.Clostridium spp. were inhibited by 0.5 µg/ml, peptostreptococci and peptococci by 0.25 µg/ml. Decaplanin was active from pH 5.5 to 7.5. Inoculum size had a minimal effect on MICs, and increased concentrations of Ca²⁺ and Mg²⁺ and 50 % serum did not alter MICs or MBCs.     

Interpretive criteria for CI-960, fleroxacin and temafloxacin susceptibility tests withHaemophilus influenzae

Haemophilus influenzae strains with varied ampicillin resistance and beta-lactamase production patterns were tested against three investigational fluorinated quinolones (CI-960, fleroxacin, temafloxacin) using Haemophilus Test Medium (HTM) and National Committee for Clinical Laboratory Standards (NCCLS) methods. The disk diffusion zones and MICs were compared and regression statistics and scattergrams generated. The rank order of the agents according to activity againstHaemophilus influenzae was CI-960 (MIC50 0.002 µg/ml) > temafloxacin (MIC50 0.015 µg/ml) > fleroxacin (MIC50 0.03 µg/ml). The recommended susceptibility interpretive criteria for the 5-µg disks of each drug were: for CI-960 23 mm (MIC correlate 1 µg/ml); for fleroxacin 19 mm (MIC correlate 2 µg/ml); and for temafloxacin 16 mm (MIC correlate 2 µg/ml). All recentHaemophilus influenzae isolates tested were susceptible to these potent fluoroquinolones and no interpretive errors were observed.     

Geographic variation in the susceptibilities of invasive isolates of Candida glabrata to seven systemically active antifungal agents: a global assessment from the ARTEMIS Antifungal Surveillance Program conducted in 2001 and 2002

We examined the susceptibilities to amphotericin B, flucytosine, fluconazole, posaconazole, ravuconazole, voriconazole, and caspofungin of 601 invasive isolates of Candida glabrata and grouped the isolates by geographic location: North America (331 isolates), Latin America (58 isolates), Europe (135 isolates), and Asia-Pacific (77 isolates). Caspofungin (MIC at which 90% of isolates tested are susceptible [MIC(90)], 0.12 microg/ml; 100% of strains are susceptible [S] at a MIC of 相似文献   

In vitro susceptibility ofHelicobacter pylori to the new oral cephalosporins cefpodoxime,ceftibuten and cefixime

The in vitro activity against 30Helicobacter pylori strains of three new third generation cephalosporins, cefpodoxime, ceftibuten and cefixime, which can be administered orally, was determined using an agar dilution technique under microaerophilic conditions. The MIC50 and MIC90 of cefpodoxime was 0.5 and 4.0 µg/ml respectively, of ceftibuten 2.0 and 8.0 µg/ml, and of cefixime 0.06 and 0.5 µg/ml. All antibiotics showed good activity againstHelicobacter pylori, cefixime having the highest activity of the three agents.     

Comparative in vitro activity of the new oral macrolide azithromycin

The in vitro activity of the new oral macrolide azithromycin was compared with that of erythromycin against gram-positive and gram-negative aerobic and anaerobic bacteria. Ninety percent of hemolytic streptococci groups A and B, andStreptococcus pneumoniae were inhibited by 0.5 µg/ml. Activity of azithromycin was similar to that of erythromycin; erythromycin-resistant staphylococci and streptococci were not inhibited. Azithromycin was more active than erythromycin againstHaemophilus influenzae (MIC90 1 µg/ml) andNeisseria gonorrhoeae. It inhibitedCampylobacter spp. andPasteurella multocida, and had an MIC50 of 8 µg/ml forEscherichia coli, Salmonella spp.,Shigella spp. andYersinia enterocolitica compared to an erythromycin value of > 64 µg/ml.     

In vitro activity of OPC-17116 compared to other broad-spectrum fluoroquinolones

The in vitro activity of OPC-17116 was compared to that of five similar fluoroquinolones (ciprofloxacin, enoxacin, norfloxacin, ofloxacin and temafloxacin). A total of 700 isolates from recent cases of clinical bacteremia were tested. Fifty additional stock strains with well-characterized resistance mechanisms were also processed. The minimal concentrations inhibiting 90 % of strains (MIC90) ofEnterobacteriaceae species were for OPC-17116 0.015–0.5 µg/ml and for ciprofloxacin 0.015–0.25 µg/ml.Moraxella catarrhalis, Haemophilus influenzae andNeisseria gonorrhoeae were very susceptible to OPC-17116 (MIC90 0.015 µg/ml) thus being fourfold more active than ciprofloxacin. For all -hemolytic streptococci and pneumococci OPC-17116 MICs were 0.5 µg/ml. The most resistant enteric bacilli were among theCitrobacter freundii andProvidencia rettgeri strains (MIC90 0.5 µg/ml).Pseudomonas aeruginosa strains were comparably susceptible to OPC-17116 (MIC90 0.5 µg/ml). Low pH and CO₂ incubation had an adverse effect on OPC-17116 MICs, and resistance development was documented among current clinical isolates of staphylococci, pseudomonas and someEnterobacteriaceae.     

In vitro activity of biapenem against beta-lactamase producingEnterobacteriaceae

The activity of biapenem was compared with that of imipenem and cefotaxime against 108 strains of -lactamase producingEnterobacteriaceae. Biapenem and imipenem were very active, inhibiting 90 % of the strains at a concentration of 0.5 µg/ml. Both carbapenems were very active against plasmidic -lactamase producers, with MIC90s below 1 µg/ml. However, the MIC90 of biapenem for cephalosporinase producers was 1 µg/ml. Against strains producing extended-spectrum -lactamases, biapenem exhibited better activity against TEM-type producers (MIC90 0.25 µg/ml) than against SHV-type producers (MIC90 0.5 µg/ml). Overall, the in vitro antibacterial activity of biapenem is similar to that of imipenem.     

Caspofungin activity against clinical isolates of fluconazole-resistant Candida

A total of 7,837 clinical isolates of Candida were tested against fluconazole, and 351 resistant (fluconazole MIC >/=64 micro g/ml) isolates were identified (4% of the total tested). All fluconazole-resistant isolates were inhibited by caspofungin at concentrations that can be exceeded by standard doses (MIC at which 90% of the isolates were inhibited, 1 micro g/ml; 99% of the MICs were 相似文献   

Interpretive criteria and quality control parameters for determining bacterial susceptibility to fosfomycin tromethamine

Studies with fosfomycin tromethamine disks containing 200 µg of fosfomycin and 50 µg of glucose-6-phosphate confirmed the following zone diameter criteria for the NCCLS method: 12 mm for resistant (MIC256 µg/ml), 13–15 mm for intermediate (MIC 128 µg/ml) and 16 mm for susceptible (MIC64 µg/ml). Additional studies defined acceptable MIC and zone diameter ranges for the following quality control strains:Escherichia coli ATCC 25922, MIC 0.5 to 4.0 µg/ml, zone diameter 23 to 29 mm;Staphylococcus aureus ATCC 25923, zone diameter 26 to 32 mm;Pseudomonas aeruginosa ATCC 27813, MIC 2.0 to 8.0 µg/ml; andEnterococcus faecalis, ATCC 29212, MIC 16 to 64 µg/ml.     

Candida krusei, a multidrug-resistant opportunistic fungal pathogen: geographic and temporal trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005

Candida krusei is well known as a fungal pathogen for patients with hematologic malignancies and for transplant recipients. Using the ARTEMIS Antifungal Surveillance Program database, we describe geographic and temporal trends in the isolation of C. krusei from clinical specimens and the in vitro susceptibilities of 3,448 isolates to voriconazole as determined by CLSI (formerly NCCLS) disk diffusion testing. In addition, we report the in vitro susceptibilities of bloodstream infection isolates of C. krusei to amphotericin B (304 isolates), flucytosine (254 isolates), anidulafungin (121 isolates), caspofungin (300 isolates), and micafungin (102 isolates) as determined by CLSI broth microdilution methods. Geographic differences in isolation were apparent; the highest frequency of isolation was seen for the Czech Republic (7.6%) and the lowest for Indonesia, South Korea, and Thailand (0 to 0.3%). Overall, 83% of isolates were susceptible to voriconazole, ranging from 74.8% in Latin America to 92.3% in North America. C. krusei was most commonly isolated from hematology-oncology services, where only 76.7% of isolates were susceptible to voriconazole. There was no evidence of increasing resistance of C. krusei to voriconazole from 2001 to 2005. Decreased susceptibilities to amphotericin B (MIC at which 90% of isolates were inhibited [MIC₉₀], 4 μg/ml) and flucytosine (MIC₉₀, 16 μg/ml) were noted, whereas 100% of isolates were inhibited by ≤2 μg/ml of anidulafungin (MIC₉₀, 0.06 μg/ml), micafungin (MIC₉₀, 0.12 μg/ml) or caspofungin (MIC₉₀, 0.25 μg/ml). C. krusei is an uncommon but multidrug-resistant fungal pathogen. Among the systemically active antifungal agents, the echinocandins appear to be the most active against this important pathogen.     

Variable antifungal susceptibility of wild-typeCandida albicans phenotypes from neutropenic hosts

The aim of the present study was to investigate the relationship between phenotypes ofCandida albicans strains isolated from clinical specimens and susceptibility of the strains to two antifungal agents, itraconazole and fluconazole. Oropharyngeal, gastrointestinal tract, and urogenital tract specimens were collected from 131 neutropenic patients withCandida infection who had received no previous prophylactic treatment. The most frequent species isolated wasCandida albicans, followed byCandida glabrata,Candida tropicalis, Candida krusei, andCandida parapsilosis. Each of the 44Candida albicans strains recovered was found to express one of four phenotypes: smooth, irregular, fuzzy or stipple. Mean minimum inhibitory concentrations (MICs) of itraconazole and fluconazole as determined by the microdilution method and the E-test were consistently higher forCandida albicans strains expressing the stipple phenotype. The mean MICs for the four phenotypes of theCandida albicans strains ranged between 0.35 g/ml and 2.41 g/ml for itraconazole and 2.78 g/ml and 5.2 g/ml for fluconazole. Antifungal susceptibility of the stipple phenotype requires careful appraisal, especially in patients clinically unresponsive to azole chemotherapy or in cases of life-threatening, deepseatedCandida infections.     

In-vitro susceptibility testing by agar dilution method to determine the minimum inhibitory concentrations of amphotericin B, fluconazole and ketoconazole against ocular fungal isolates

Purpose: To standardize in-vitro antifungal susceptibility testing by agar dilution method to find out the minimum inhibitory concentration (MIC) of amphotericin B, fluconazole and ketoconazole on ocular fungal isolates. Methods: A total of 180 ocular fungal isolates (130 filamentous fungi and 50 yeasts) were included. The antifungal drugs such as amphotericin B (0.0625-8 μg/mL), fluconazole (0.2-819.6 μg/mL) and ketoconazole (0.025-6.4 μg/mL) were incorporated in doubling dilutions in the yeast nitrogen base medium. The MIC was determined as the lowest concentration of the antifungal drug preventing growth of macroscopically visible colonies on drug containing plates when there was visible growth on the drug - free control plates. Results: All 50 ocular isolates of yeast were susceptible to amphotericin B, while two (4%) and five (10%) strains were resistant to fluconazole and ketoconazole respectively. Of the 130 filamentous fungi tested, six (4.6%) were resistant to amphotericin B, 49 (37.7%) and 10 (7.6%) were resistant to fluconazole and ketoconazole respectively. Percentile 50 (MIC 50) and Percentile 90 (MIC 90) for all the three antifungal agents were calculated. Aspergillus niger, Aspergillus terreus and Candida krusei were found to be resistant to fluconazole and ketoconazole. Conclusion: This technique was found to be reliable, cost effective and easy to perform with consistent results.